Purpose To prepare biomimetic targeted nanobubbles(NBs)named IR780-RBCM@NBs and explore the ability of performing ultrasound enhancement,escaping immune surveillance and targeting tumor cells.Materials and Methods The red blood cell membrane(RBCM)was extracted from mouse blood,the IR780-RBCM@NBs were prepared by modified membrane hydration method,the physical and chemical properties of nanobubbles were detected.In vitro,self-made equipment was used to test the contrast-enhanced ultrasound imaging ability of the nanobubbles.Laser confocal fluorescence microscopy was used to observe the characteristics of the nanobubbles retaining CD47 on the RBCM surface,and further to observe the phagocytosis of the nanobubbles by macrophages and the targeting ability of the nanobubbles to different tumor cells.Results The newly prepared IR780-RBCM@NBs had the appearance of emulsion,the particle size was about(522.4±58.6)nm and the dispersity was good.It was spherical in uniform size under the microscope.IR-780 could be detected on the nanobubbles,which had the dual-mode imaging capabilities of near-infrared fluorescence imaging and contrast-enhanced ultrasound imaging.The RBCM-specific protein CD47 could be detected on the surface of the nanobubbles.The nanobubbles exhibited excellent immune phagocytic escape function and high efficiency to target different tumor cells.Conclusion Newly prepared biomimetic targeted IR780-RBCM@NBs,with good performance,can escape immune phagocytosis and efficiently target tumors,providing a new idea for molecular targeted accurate diagnosis and treatment of tumors.

Objective:To evaluate the performance of the self-developed transcranial ultrasound patch probe as well as its stability and safety in clinical applications.Methods:This study was a cross-sectional study. Fifty healthy subjects in Tangdu Hospital from October to December 2023 were randomly and equally divided into two groups using a simple randomization method. The transcranial Doppler ultrasound (TCD) examinations were performed using the self-developed transcranial ultrasound patch probe and normal TCD probe alternatively in each group from squatting to sitting and then to standing posture. Two experienced sonographers (A, B) each completed one test for the same subject using the above two different probes. The differences of the ultrasound parameters of middle cerebral artery (MCA) blood flow measured by the self-developed transcranial ultrasound patch probe and the normal TCD probe in different postures (squatting, sitting, standing) were compared. At the same time, operator satisfaction with the use of the two probes was assessed in terms of time taken to obtain satisfactory images, operational comfort, and ease of handling. In addition, the subject's comfort during the examination was examined, and the signal acquisition stability of the two probes was comprehensively evaluated.Results:There was no significant difference in detection of various ultrasound parameters of MCA between using the transcranial patch probe and the normal TCD probe (all P>0.05). The overall satisfaction of transcranial ultrasound patch probe and normal TCD probe was quite similar. The transcranial ultrasound patch probe acquired favorable and stable signals. No subjects experienced adverse events/accidents during the examination of the subjects using the transcranial ultrasound patch probe as well as the normal TCD probe.Both probes had good and stable signal acquisition. Conclusions:TCD examinations could be well performed using the transcranial ultrasound patch probe, which might provide a potential new method for real-time monitoring and evaluating of cerebral blood flow of a moving subject.

Objective:To explore the level of arterial stiffness and its influencing factors in prediabetic population.Methods:From June 2021 to June 2022, 207 prediabetes patients were prospectively and randomly recruited from the physical examination center and outpatient clinic of Tangdu Hospital of Air Force Military Medical University to be the prediabetic group and 130 healthy volunteers at the same time with the same gender and age as the healthy controls. The carotid-femoral pulse wave velocity (PWV), brachial-radial PWV, and femoral-ankle PWV were measured by an automatic ultrasonic arterial stiffness measurement technology. The common carotid artery wall intima-media thickness (IMT) and left heart function were routinely evaluated. A questionnaire was designed to investigate the subjects′ smoking, drinking, diet, staying up late, exercise and other living habits. Comparison between groups and multivariate linear regression analysis were used to analyze the relevant data.Results:The carotid-femoral PWV and common carotid artery wall IMT in prediabetic group were significantly higher than those in healthy controls [(7.10±2.00)m/s vs (6.26±1.14)m/s, (0.57±0.11)mm vs (0.51±0.08)mm; both P<0.001], but there were no significant differences in the brachial-radial PWV and femoral-ankle PWV between the two groups (both P>0.05). Multivariate linear regression analysis showed that prediabetes was an independent influencing factor in carotid-femoral PWV after adjusting for confounding factors ( P<0.001), in addition, age ( P<0.001), diastolic blood pressure ( P<0.001), staying up late ( P=0.011) and low density lipoprotein cholesterol ( P=0.022) were also the independent influencing factors of carotid-femoral PWV. Conclusions:Compared with healthy people, the stiffness of aorta is significantly increased in prediabetic people, but there is no significant change in the stiffness of peripheral arteries. Prediabetes, age, diastolic blood pressure, staying up late and low density lipoprotein cholesterol are independent influencing factors of carotid-femoral PWV.

Objective:To investigate the effect of self-made phase-change nanodroplets IR780/FA-Nds-DTX as molecular targeted ultrasound contrast agents for accurate diagnosis and combined targeted therapy of pancreatic cancer.Methods:Pancreatic cancer cell lines were cultured in vitro and 50 tumor bearing nude mouse models were established. The experimental group (IR780/ FA-NdS-DTX) and four control groups[ normal saline, Nds(FITC), FA-Nds (FITC) and IR-780] were divided to verify dual-mode targeted imaging. The imaging using the IVIS Imaging System verified the high-efficiency targeted detection ability and near-infrared fluorescence imaging of IR780/FA-Nds-DTX for tumors in vivo, phase transformation induced by low-intensity focused ultrasound and further contrast-enhanced ultrasound imaging verified the high-efficiency aggregation of IR780/FA-Nds-DTX in local tumors and accurate evaluation of tumor contour. The therapeutic effect was observed in the experimental group (IR780/FA-Nds-DTX) and four control groups (FA-Nds-IR780, FA-Nds-DTX, FA-Nds and normal saline). After low-intensity focused ultrasound irradiation for 30s induced microbubble blasting after phase transformation in each group, 808nm photothermal therapy apparatus was used to irradiate tumor area in each group. Two-dimensional ultrasound was used to monitor the changes in tumor volume in each group before and at 3 d, 9 d, 15 d after treatment, and the changes in tumor volume rate and inhibition in each group were statistically analyzed and compared.Results:The amount of IR780/ FA-Nds-DTX locally targeted aggregation was the largest, and the average fluorescence intensity of tumor in the experimental group was significantly higher than that of the control groups: IR780/ FA-Nds-DTX group compared with Nds(FITC) group[(5.12±0.69)×10 7 vs (1.06±0.23)×10 7, P<0.05], IR780/FA-Nds-DTX group compared with FA-Nds (FITC) group [(5.12±0.69)×10 7 vs (2.98±0.34)×10 7, P<0.05], IR780/FA-Nds-DTX group compared with IR-780 group [(5.12±0.69)×10 7 vs (1.54±0.42)×10 7, P<0.05], and there was no fluorescence in tumor area in saline group. Further contrast-enhanced ultrasound imaging after nanodroplet phase transformation could more accurately locate the tumor boundary. After 15 days of photothermal ablation combined with chemotherapy, the growth rate of tumor volume in the IR780/ FA-Nds-DTX treatment group was significantly lower than that in the control groups: IR780/FA-Nds-DTX group compared with FA-Nds-IR780 group[(0.105±0.075) vs (0.405±0.175), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds-DTX group [(0.105±0.075) vs (1.385±0.035), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds group [(0.105±0.075) vs (2.255±0.105), P<0.05], IR780/ FA-Nds-DTX group compared with normal saline group [(0.105±0.075) vs (2.185±0.155), P<0.05]. And the tumor inhibition rate increased significantly: IR780/ FA-Nds-DTX group compared with FA-Nds-IR780 group [(0.93±0.06) vs (0.48±0.17), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds-DTX group [(0.93±0.06) vs (-0.51±0.105), P<0.05], IR780/ FA-Nds-DTX group compared with FA-Nds group [(0.93±0.06) vs (-1.63±0.115), P<0.05], IR780/ FA-Nds-DTX group compared with normal saline[(0.93±0.06) vs (-1.35±0.245), P<0.05]. Conclusions:The self-made phase-change ultrasound contrast agents IR780/FA-Nds-DTX have good potential clinical value in targeted detection and combined therapy of pancreatic cancer with small lesions or even metastases.

Objective:To investigate the application of ultrasound imaging in evaluating the curative effect of patients with nutcracker syndrome (NCS) treated with three-dimensional(3D) printing extravascular titanium stents.Methods:From December 2015 to December 2018, a total of 41 NCS patients enrolled in the Second Affiliated Hospital of the Air Force Military Medical University to receive 3D-printing extravascular titanium stents treatment were included in this study. Ultrasound and CT angiography (CTA) were performed before and 1 week after operation to evaluate the compression of left renal vein and related hemodynamic changes.Results:Before the operative, the ultrasound examination showed that the angle between the abdominal aorta and superior mesenteric artery was (21.29±4.53)°, which was significantly improved in 1 week after treatment [(47.42±7.45)°, P<0.001]. Left renal vein was significantly compressed before treatment, with the smallest inner diameter of (1.51±0.49)mm and its peak blood flow velocity was (143.92±50.40)cm/s. Postoperative ultrasound images showed the significant expansion of left renal vein and no high velocity blood flow was observed. Ultrasound examination also showed that the diameter of left renal vein at renal hilum, blood flow velocity at renal hilum and inner diameter of spermatic vein were significantly improved after treatment ( P<0.001). Similar to ultrasound results, CTA also found that the angle between abdominal aorta and superior mesenteric artery increased significantly after treatment[(17.59±4.56)° vs (52.27±9.01)°, P<0.001]. CTA also showed the left renal vein was compressed before treatment, with the smallest inner diameter of (2.09±0.86)mm, and it was significantly expanded after operation. The inner diameter of left renal vein at renal hilum was also significantly reduced after treatment ( P<0.001). Conclusions:Ultrasound imaging can effectively evaluate the LRV compression and related hemodynamic changes before and after 3D printed stent implantation treatment in NCS patients and provide a reliable method to evaluate its clinical efficacy for these patients.

Objective:To prepare a dual targeting nanobubble both for HER2 target and cancer cell target, and compare the targeting ability with single targeting nanobubble either with HER2 targeting or cancer cell targeting ability in vitro.Methods:Nanobubbles(NBs) were prepared using the modified thin film hydration method and then connected with IR783 directly (NBs-IR783), HER2 antibody Affibody by avidin-biotin method (NBs-Affibody), or both of them (IR783-NBs-Affibody). The size distribution, stability, and biosafety of these contrast agents were observed. Flow cytometry and immunofluorescence were applied to compare the binding rate of these NBs against HER2 positive breast cancer cell in vitro.Results:The average size of NBs-Affibody, NBs-IR783 and IR783-NBs-Affibody was (538.4±95.8)nm, (551.8±114.8)nm, and (482.7±54.3)nm, respectively. The binding rate for HER2 positive cell was 26.6%, 97.6%, 84.5%, while for HER2 negative cell was 5.4%, 99.9% and 99.3%, respectively. The results of dual-labeled flow cytometry showed that the binding rate of IR783-NBs-Affibody mediated by IR783 to HER2 positive breast cancer cells were 79.5% and Affibody mediated HER2 targeting binding rate were 19.4%. However, NBs-IR783 only showed IR783-mediated tumor targeted binding without HER2 targeting ability with binding rate of 2.3%.Conclusions:The prepared IR783-NBs-Affibody has the dual targeting ability for HER2 positive breast cancer cell, which is superior to the single targeting NBs (NBs-Affibody and NBs-IR783). IR783-NBs-Affibody is optimal to meet the imaging requirements of tumor heterogeneity.

Objective To explore the value of transrectal elastography and contrast-enhanced ultrasound in evaluation of the efficacy of neoadjuvant therapy for rectal cancer.Methods Forty patients with final diagnosis of advanced(T≥3) rectal cancer were respectively examined with transrectal ultrasound (TRUS),endorectal elastography and contrast-enhanced ultrasound(CEUS) before and after neoadjuvant therapy(NET).The tumor size,strain ratio and quantitative parameters of contrast-enhanced ultrasound including arrival time(AT),time-to-peak (TTP),peak intensity(PI) and area under the curve(AUC) were recorded and compared before and after NET.In addition,the TRUS stages and postoperative pathological diagnosis were compared after NET.Results ①There were significant decreases in tumor size and strain ratio after the therapy compared with pre-therapy in all these patients(t =-6.13,P ＜0.001;t =-24.92,P ＜ 0.001).②PI and AUC were lower after NET than those of pre-therapy and the differences were significant(t =-9.66,P =0.001;t =-13.58,P ＜0.001).However,the changes of AT and TTP were no statistical significances (t =-1.17,P =0.307;t =-1.26,P =0.275).③The accuracys of preoperative TRUS for T stage and N stage of tumor evaluated according to pathology were respectively 75.0 ％ (30/40,Kappa =0.593,P =0.000) and 72.5 ％ (29/40,Kappa =0.396,P =0.009).Conclusions Transrectal elastography and contrast-enhanced ultrasound can reflect the pathological changes and perfusion characteristics of lesions in a certain extent and have high value in clinical therapy.

Objective To observe the blood flow changes of left ventricular cavity and quantify the energy loss (EL) and circulation of left ventricular during systole and diastole in patients with dilated cardiomyopathy(DCM) via vector flow mapping(VFM).Methods Thirty-six healthy volunteers and 32DCM patients were enrolled.According to the severity of mitral regurgitation(MR),DCM patients were divided into two groups.The quantitative parameters,including average energy loss(EL-base,EL mid,EL-apex) and circulation (vortex quantity,vortex area,circulation) were measured in the different periods of VFM imaging mode in apical four-chamber view,apical three-chamber view and apical two-chamber view respectively.The difference of parameters was evaluated between different groups during the different periods.The early transmitral valve blood flow velocity E,the late transmitral valve blood flow velocity A,the ratio of early transmitral valve blood flow velocity to the early diastolic mitral valve velocity E/e,the ratio of early transmitral valve blood flow velocity to the late transmitral valve blood flow velocity E/A and Tei index were derived via dual-Doppler imaging technology.Meanwhile,the correlation between VFM parameters with E,A,E/A,E/e or Tei index was also analyzed.Results ①The level of EL were decreased significantly among EL-mid and EL-apex during early diastole,EL-mid during mid-systole,EL-mid and EL-apex during late-systole (P ＜0.05),when compared with the control group.The vortex quantity,vortex area and circulation during early diastole and the vortex area and circulation during atrial contraction period were significantly different between two groups (all P ＜ 0.05).As for mid-diastole,only vortex area showed significant difference (P ＜0).01).(②) When compared with different grades of MR in DCM patients,the level of all segments EL during diastole and EL-base during systole increased with severity of MR(P ＜0.05).The circulation during diastole also increased with the severity of MR(P ＜0.05).③The vortex area and circulation had positive correlation with E/e during diastole in all subjects(all P ＜0.05).The vortex area during atrial contraction period and early diastole had positive correlation with E/A and Tei index in all subjects(r =0.630,0.345,0.468,0.316,0.663,0.264,respectively,allP ＜0.01).EL-mid during late-systole were negatively correlated with LV end diastolic volume,end systolic volume,but positively correlated with ejection fraction in all subjects(r =0.335,-0.312,0.340,respectively,all P ＜0.05).While,there was positive correlation between E/A with the basal segment of mid-diastole(r =0.376,P ＜0.01).Conclusions The visualization of hydromechanics inside the heart of DCM patients could be directly accomplished by VFM,which can provide a new method for diagnosis and evaluation of DCM.

Objective To compare the respective diagnostic efficiency for breast cancer with ultrasound diffusion optical imaging (DOI),ultrasonic elastography (UE),contrast-enhanced ultrasound (CEUS),X-ray mammography(XRM),magnetic resonance imaging (MRI),and combinations of these imaging modalities.Methods Seventy-five breast lesions were collected.These lesions were confirmed by surgery and histopathology.All of breast lesions were examined ultrasound,mammography and enhancedMRI examinations before surgical excision.The specificity,sensitivity,positive predictive value and negative predictive value of each modality were compared.Results The sensitivities and the diagnostic negative predictive values for MRI + US + XRM (97.44％,96.15％),CEUS (92.31％,90.63％) and MRI (94.87 ％,92.86％) were significantly higher than those for XRM (74.36 ％,71.43 ％),respectively.The sensitivity for DOI + CEUS + UE was the same as one for CEUS,they were not significantly higher than those for UE and DOI (P ＞0.05),while they were significantly higher than that for XRM (P ＜0.05).The kappa values for DOI,UE,CEUS,USG(UE + DOI + CEUS),XRM,MRI and MRI + US + XRM were 0.678,0.624,0.732,0.705,0.439,0.677 and 0.676,respectively.Conclusions Different imaging modalities have themselves advantages to diagnose malignant or benign lesions.CEUS,MRI and combinations of these imaging modalities have highly important clinical values in breast disease diagnosis.